The research outlined in this proposal is aimed at developing and testing four new classes of synthetic carriers for antitumor drugs. Over the past few years there has been a growing belief that liposomes (phospholipid bilayer vesicles) as carriers of antitumor drugs may offer the following benefits in cancer chemotherapy: (1) promotion of drug passage across cell membranes, (2) increased plasma lifetime of drugs, (3) increased targeting to desired tissues and to tumor cells and (4) retardation of drug catabolism. The basic premise which umderlies our work is that liposome--drug instability in the form of lipid exchange processes, direct removal and net transfer of lipids from vesicles, uncontrolled leakage of entrapped drugs and vesicle--vesicle fusion, severly limits the practical use of the lipid carriers currently under consideration by clinicians. Each of the synthetic carriers which we will synthesize has been specifically designed to achieve (1) greater intrinsic stability, (2) slower and more controllable time-release action, (3) preferred endocytotic and adsorption modes of interaction with cells and (4) greater targeting potential. The broad objective of this program is to expand the durg carrier concept by developing new classes of carriers that could be used to augment current methods in the chemotherapeutic treatment of neoplastic disease.